Recently, Lemborexant, a dual orexin receptor antagonist originally developed by Eisai, was approved for marketing by the National Medical Products Administration, marking the official entry of China's insomnia treatment field into the "dual orexin antagonist era."

Global sales exceeded 2.6 billion yuan

Unlike traditional sedative hypnotic drugs, Lebrexan competitively binds to orexin type 1 receptor (OX1R) and type 2 receptor (OX2R), precisely inhibiting orexin-mediated wakefulness drive, thereby inducing natural sleep. In addition, unlike traditional GABA-A hypnotic drugs that inhibit rapid eye movement sleep (REM), Lebrexan can simultaneously extend the duration of non-rapid eye movement sleep (NREM) and REM, optimizing sleep structure to make it closer to the physiological sleep state.

Clinical trials have shown that Lebrexan has a mild effect on patients' memory and cognitive function, and does not significantly interfere with daytime activities (especially driving and other behaviors that require mental concentration). Studies have shown that the drug has no physical dependence, and users who stop taking it for a long time (12 months) will not have withdrawal symptoms or insomnia rebound, and no reports of addiction have been found since it was launched.

Currently, Lebrexan has been launched in more than 20 countries and regions around the world. In Japan, the drug has been included in the "Japanese Expert Consensus on the Treatment of Insomnia Disorders" and has become a recommended double-first-line drug for difficulties in initiating and maintaining sleep. In China, Lebrexan has previously passed the "Hong Kong and Macao Drug and Medical Device Access" policy and has been used first in some hospitals in the Greater Bay Area.

Eisai's financial report shows that Lebrexan will achieve global sales of 53.8 billion yen (equivalent to about 2.69 billion yuan) in fiscal year 2024, becoming the second largest pillar of Eisai's product revenue after Lenvima, a drug for Alzheimer's disease. With its launch in China, relying on the huge domestic market for insomnia patients, Lebrexan is expected to usher in a new peak of commercial growth.

Note: This article is for information exchange purposes only. The views expressed in this article do not represent the position of Yaozhi.com, nor are they treatment recommendations. If you need treatment guidance, please go to a regular hospital for treatment.

Huge market potential

The 2025 China Sleep Health Survey Report released by the China Sleep Research Society in March 2025 shows that the sleep disturbance rate of people aged 18 and above in China is 48.5%, among which the sleep disturbance rate of women is 51.1%, higher than the 45.9% of men. With the increase of age, the sleep disturbance rate shows an increasing trend, and the sleep disturbance rate of people aged 65 and above is the highest, reaching 73.7%.

According to Frost & Sullivan data, in China, the number of adults suffering from insomnia increased from 250 million to 270 million from 2016 to 2020, and is expected to reach 300 million in 2024 and 330 million in 2030. During the same period, the market size of insomnia drugs increased from 9.84 billion yuan to 11.7 billion yuan, and is expected to reach 15.12 billion yuan and 21.19 billion yuan in 2025 and 2030, respectively. Debon Securities pointed out that in 2022, the market size of insomnia chemical drugs in China was 4.2 billion yuan, a year-on-year increase of 18.9%, of which benzodiazepines had sales of 1.48 billion yuan (the highest proportion), and the market growth potential was significant.

At present, the drugs used in clinical treatment of insomnia in China mainly fall into two categories: one is benzodiazepine sedative hypnotic represented by diazepam, estazolam, and clonazepam; the other is non-benzodiazepine sedative hypnotic such as zolpidem, zaleplon, and eszopiclone.

These drugs have been on the market in China for more than 20 years, and there are abundant generic drugs on the market. Among them, benzodiazepines are gradually being replaced by non-benzodiazepines in clinical applications due to their widespread adverse reactions such as drug resistance, dependence and addiction.

Due to the strict control policy of insomnia treatment drugs being included in the national second-class psychotropic drugs, the development and marketing of new drugs have been lagging behind for a long time. Since the approval of dexamethasone in 2007, the domestic insomnia new drug market has experienced a 16-year blank period. It was not until December 2023 that Beijing New Pharmaceutical's innovative drug Didacidin Capsules were approved for marketing for the short-term treatment of patients with insomnia disorders, which ended this situation.

Didacidin Capsules are new benzodiazepine receptor agonists that bind to the α1 subtype of GABAa receptors, mildly activate receptors and inhibit the central nervous system to induce sleep. Unlike traditional full activators, its mechanism of action avoids the side effects of deep inhibition caused by over-activation of receptors. It has the advantages of falling asleep quickly, maintaining sleep all night, not affecting sleep structure, not easy to become addicted, and good tolerance among the elderly, filling the gap in medical needs in the field of sedation and hypnosis.

The drug was developed by Roche and later authorized to Evotec for global development. In 2010, Beijing New Pharmaceuticals and Evotec reached a cooperation agreement, and Didacillin was approved for marketing in China in December 2023.

Didacil performs well in the treatment of primary insomnia in adults. For adult patients, compared with placebo, 1.5 mg and 2.5 mg of didacil prolonged total sleep time by 33.1 and 45 minutes, respectively, reduced awakenings after falling asleep by 16.7 and 25.7 minutes, and reduced the number of awakenings by 1.2 and 2.6 times. Both doses significantly improved the patients' sleep quality. In addition, didacil also performs well in the treatment of primary insomnia in the elderly and can significantly reduce the daytime physiological sleep tendency of elderly patients.

According to the "Guidelines for the Diagnosis and Treatment of Insomnia in Chinese Adults" (2023 edition), the current preferred drugs for insomnia in China include dual orexin receptor antagonists, non-benzodiazepine drugs and new benzodiazepine receptor agonists.

Note: This article is for information exchange purposes only. The views expressed in this article do not represent the position of Yaozhi.com, nor are they treatment recommendations. If you need treatment guidance, please go to a regular hospital for treatment.

New products are expected to be approved one after another

Benzodiazepines are the mainstream sleeping pills in the market. Although they can quickly induce sleep, long-term use can easily lead to drug dependence, and are often accompanied by residual effects such as dizziness and fatigue the next day. It is particularly noteworthy that if dependents suddenly stop taking the drug, they may experience withdrawal syndrome, which manifests as rebound aggravation of insomnia, limb numbness, and even mental symptoms such as delusions, which greatly limits their long-term clinical application.

Orexin is a key neuropeptide secreted by the hypothalamus. It maintains wakefulness mainly by activating the central arousal pathway and is involved in physiological processes such as feeding, metabolism and blood pressure regulation. Orexin receptor antagonists developed for this target can be divided into three categories: OX1R antagonists (mainly used for the treatment of anxiety and addiction), selective OX2R antagonists and dual OX1/2R antagonists (DORAs). Among them, DORAs precisely inhibit the overactive wakefulness signals of insomnia patients by blocking the binding of orexin A/B to receptors, thereby achieving the mechanism of "sleep aid on demand" and avoiding the extensive inhibition of the central nervous system by traditional sedatives.

The "Guidelines for the Diagnosis and Treatment of Insomnia in Chinese Adults (2023 Edition)" clearly states that although some non-benzodiazepines (such as zolpidem and eszopiclone) have evidence for long-term use, short-term use (generally no more than 4 weeks) is still recommended in view of the potential risk of addiction, and long-term use requires regular evaluation. As a new generation of insomnia treatment drugs, DORAs have the unique advantages of "no clear evidence of drug dependence, long-term use, and no significant rebound insomnia after discontinuation of the drug."

Suvorexant was developed by Merck and was approved by the FDA in 2014 for the treatment of difficulty falling asleep and maintaining sleep. It is the world's first orexin receptor antagonist. Suvorexant's sales were $318 million in 2021, but have been declining since 2020, falling to $258 million in 2022. In China, Merck has deployed related patents, of which the drug patent is expected to expire in 2027 and the formulation patent will last until 2033.

Following Suvorexant, Lemborexant, developed by Eisai, was approved by the FDA in December 2019 for adults with insomnia caused by difficulty falling asleep or maintaining sleep. It is currently available in Japan, Canada, Australia and other countries. In China, Lemborexant has not yet been included in the management scope of Class II psychotropic drugs.

Daridorexant, developed by Swiss company IDORSIA, was approved by the FDA in January 2022. In November of the same year, Innovent and IDORSIA reached an exclusive licensing agreement to obtain the rights to clinical development and commercialization of the drug in China. In July 2024, Innovent announced that the application for Daridorexant to be marketed in China was accepted by the State Food and Drug Administration, which means that this orexin receptor antagonist has entered the countdown for market review in China. Relying on Innovent's market experience in the neurological field (such as the sales base of Xinbixin injection), the drug is expected to occupy a place in the domestic insomnia treatment market in the future.
In the R&D pipeline of innovative insomnia drugs, orexin receptors are the current mainstream target, and some drugs have entered the key clinical stage:

Fazamorexant (YZJ-1139) from Yangtze River Pharmaceuticals: As a highly effective dual orexin receptor antagonist, it improves sleep by inhibiting the arousal pathway, significantly accelerating the speed of falling asleep and prolonging sleep time. Currently in Phase 3 clinical trials for the treatment of insomnia, Phase 2 data showed that the drug can increase sleep efficiency to a healthy level in a dose-dependent manner, and has no obvious central nervous system side effects compared to placebo, and has extremely low next-day residual effects, showing good safety and effectiveness.

Takeda Pharmaceutical's TAK-360: An oral OX2R agonist that focuses on the treatment of narcolepsy type 2 and idiopathic hypersomnia. It improves abnormal wakefulness states by regulating the orexin pathway, forming a differentiated layout for insomnia treatment.

Hansoh Pharmaceuticals HS10506: A novel high-affinity selective OX2R antagonist in Phase 1/2 clinical trials. Studies in healthy subjects showed good safety and tolerability, ideal pharmacokinetic characteristics, and the expected drowsiness effect at a single oral dose of up to 60 mg.

HEC83518 of East Sunshine Pharmaceutical: Obtained clinical trial approval from NMPA in January 2020 for the treatment of insomnia and is currently in Phase 1 clinical trials.

Conclusion

As the pace of modern society accelerates and pressure continues to increase, sleep health issues are becoming increasingly prominent, and the number of people diagnosed with insomnia worldwide is increasing year by year. Although the Chinese insomnia drug market started late and was limited in scale in the early stages, with a high degree of industry concentration, many innovative pharmaceutical companies are accelerating the development and launch of generic and innovative drugs.

In terms of drug development, orexin receptor antagonists have shown the potential to become the "next blockbuster product". This type of drug works by precisely regulating the wakefulness-sleep balance pathway, and has significant differentiation advantages compared to traditional insomnia treatment drugs (such as benzodiazepines and non-benzodiazepines).

https://news.yaozh.com/archive/45554.html